Ocular Manifestations of Myotonic Dystrophy
Myotonic dystrophy (DM) is a multi-system disease characterized by myopathy, myotonia, and other multi-organ manifestations. It is a nucleotide repeat disease with autosomal dominant inheritance. There are two major forms of DM: Myotonic dystrophy 1 (DM1), historically termed Steinert’s disease, and myotonic dystrophy 2 (DM2).
The prevalence of DM has previously been estimated in European populations at around 1 in 8000. However, more recent genetic studies have suggested that the true prevalence may be much higher, with mutational frequency identified in as many as 1 in 2,760.
The systemic clinical features of DM1 are numerous and include skeletal muscle weakness, muscle pain, myotonia, cardiac abnormalities, impaired respiratory function, sleep disturbance, endocrine abnormalities, and cognitive impairment. In DM2, muscle weakness, pain, and myotonia are common, while other systemic features tend to be less frequent and milder in severity.
Muscle weakness and myotonia resulting from DM can cause associated oculomotor abnormalities, including ophthalmoplegia, extraocular muscle myotonia, and blepharoptosis or brow ptosis. Isolated ophthalmoplegia is a relatively uncommon symptom of DM but a variety of patterns have been reported in DM patients. Abnormalities in saccadic velocity have also been noted in DM, likely due to extraocular muscle myotonia which is more pronounced after prolonged fixation. Myogenic blepharoptosis and brow ptosis from weakness of the levator palpebrae superioris and frontalis muscles, respectively, are common in DM.
Miosis, usually evident as impaired pupillary dilation following administration of pharmacologic dilating agents, has been observed in DM patients. Although the pathophysiology has not been fully elucidated, it has been theorized to be due to underlying dilator smooth muscle dysfunction.
Low intraocular pressure has frequently been observed in DM patients. In one study, DM patients had a mean IOP about 23% lower than control eyes, a difference which could not be accounted for by corneal abnormalities. In one study, ciliary body detachment was observed in all DM1 patients studied, suggesting a possible etiology for hypotony in this population.
Fuchs’ Endothelial Corneal Dystrophy
The association between DM1 and Fuchs’ endothelial corneal dystrophy (FECD) was described relatively recently after several members of a cohort of DM patients were noted to also have corneal abnormalities consistent with FECD. FECD is most closely associated with CTG trinucleotide repeat expansion in the TCF4 gene of chromosome 18. However, this trinucleotide expansion is not common in DM patients. Further studies have instead found that DMPK trinucleotide expansion, which is the causative mutation in DM1, can also cause FECD clinical disease, likely through RNA-mediated toxicity. The frequency of FECD in DM1 patients has been estimated to be as high as 46%, making this an important and newly recognized ocular manifestation.
Cataracts are the most frequent ocular manifestation of DM, common in both DM1 and DM2. Early-onset posterior subcapsular cataract, usually described as a “snowflake” or Christmas-tree cataract,” is classically associated with DM. This manifestation can be the first presenting symptom for DM2 patients in particular and is common in DM1 patients as well.
Pigmentary retinal changes in DM patients usually resemble a pattern dystrophy with butterfly-like macular changes. These can have a variable appearance and are not a consistent finding in either DM1 or DM2.
In most cases, DM is diagnosed clinically in the setting of intellectual disability, muscle pain, or muscle weakness. Genetic testing for CTG repeats in DMPK is confirmatory for DM1 as is CCTG expansion in CNPB for DM2. Genetic testing has largely replaced EMG and muscle biopsy in the initial diagnosis of DM, although these modalities may also be helpful in certain atypical cases. Electrocardiography is critical to assess for cardiac conduction defects in all DM patients.
Due to its multisystem manifestations, DM should be managed in a multi-disciplinary manner in collaboration with cardiac, pulmonary, neurologic, and endocrine sub-specialists. Currently, no disease-modifying therapy for DM exists, so management is focused on symptoms.
Ophthalmic management of DM consists largely of treatment of ocular sequelae. Cataracts that are visually significant, for example, should be treated with surgical cataract extraction. Similarly, symptomatically significant oculomotor abnormalities, such as blepharoptosis or brow ptosis, can be treated with surgical repair. Strabismus surgery rarely is indicated.
- Udd B, Krahe R. The myotonic dystrophies: molecular, clinical, and therapeutic challenges. Lancet Neurol. 2012;11(10):891-905.
- Suominen T, Bachinski LL, Auvinen S, et al. Population frequency of myotonic dystrophy: higher than expected frequency of myotonic dystrophy type 2 (DM2) mutation in Finland. Eur J Hum Genet. 2011;19(7):776-782.
- Brook JD, McCurrach ME, Harley HG, et al. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3’ end of a transcript encoding a protein kinase family member. Cell. 1992;68(4):799-808.
- Liquori CL, Ricker K, Moseley ML, et al. Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science. 2001;293(5531):864-867.
- Na S, Lee ES, Kim YD, Lee TK. Slowly Progressive Ophthalmoplegia as a Presenting Symptom of Myotonic Dystrophy Type 1. J Neuroophthalmol. 2021;41(4):e741-e742.
- Azuara-Blanco A, Kat LJ, Arkfeld DF, Walsh TJ. Myotonic dystrophy mimicking bilateral internuclear ophthalmoplegia. Neuroophthalmology. 1997;17(1):11-14.
- Thiriez C, Vignal C, Papeix C, Yaici S, Vidailhet M, Roze E. Ophthalmoplegia as the presenting muscle-related manifestation of myotonic dystrophy. Rev Neurol . 2010;166(5):538-541.
- Versino M, Rossi B, Beltrami G, Sandrini G, Cosi V. Ocular motor myotonic phenomenon in myotonic dystrophy. J Neurol Neurosurg Psychiatry. 2002;72(2):236-240.
- Kang MJ, Yim HB, Hwang HB. Two cases of myotonic dystrophy manifesting various ophthalmic findings with genetic evaluation. Indian J Ophthalmol. 2016;64(7):535-537.
- Alon M, Korczyn AD. Pupillary responses and blink reflex in myotonic dystrophy. Clin Auton Res. 1992;2(1):17-19.
- Kesler A, Berkner L, Sadeh M, Levite R, Varssano D. Is intraocular pressure in myotonic dystrophy patients spuriously low? Isr Med Assoc J. 2008;10(10):699-701.
- Rosa N, Lanza M, Borrelli M, et al. Low intraocular pressure resulting from ciliary body detachment in patients with myotonic dystrophy. Ophthalmology. 2011;118(2):260-264.
- Gattey D, Zhu AY, Stagner A, Terry MA, Jun AS. Fuchs endothelial corneal dystrophy in patients with myotonic dystrophy: a case series. Cornea. 2014;33(1):96-98.
- Mootha VV, Hussain I, Cunnusamy K, et al. TCF4 Triplet Repeat Expansion and Nuclear RNA Foci in Fuchs’ Endothelial Corneal Dystrophy. Invest Ophthalmol Vis Sci. 2015;56(3):2003-2011.
- Vinod Mootha V, Hansen B, Rong Z, et al. Fuchs’ Endothelial Corneal Dystrophy and RNA Foci in Patients With Myotonic Dystrophy. Invest Ophthalmol Vis Sci. 2017;58(11):4579-4585.
- Kidd A, Turnpenny P, Kelly K, et al. Ascertainment of myotonic dystrophy through cataract by selective screening. J Med Genet. 1995;32(7):519-523.
- Papadopoulos C, Kekou K, Xirou S, Kitsiou-Tzeli S, Kararizou E, Papadimas GK. Early onset posterior subscapular cataract in a series of myotonic dystrophy type 2 patients. Eye . 2018;32(3):622-625.
- Pagoulatos D, Kapsala Z, Makri OE, Georgakopoulos CD. Christmas tree cataract and myotonic dystrophy type 1. Eye . 2018;32(11):1794-1795.
- Kirkegaard-Biosca E, Berges-Marti M, Azarfane B, Cilveti E, Distefano L, García-Arumí J. Fundus flavimaculatus-like in myotonic dystrophy: a case report. BMC Ophthalmol. 2021;21(1):240.